AR-A014418

Bezeichnung:AR-A014418

CAS-Nr487021-52-3

Englisch Name:AR-A014418

CBNumberCB9497883

SummenformelC12H12N4O4S

Molgewicht308.31

MOL-Datei487021-52-3.mol

AR-A014418 physikalisch-chemischer Eigenschaften

Schmelzpunkt	208-210?C (dec.)
Dichte	1.464±0.06 g/cm3(Predicted)
storage temp.	2-8°C
Löslichkeit	DMSO: ≥20mg/mL, clear, light yellow
Aggregatzustand	Yellow solid
pka	5.80±0.70(Predicted)
Farbe	off-white to tan
Sensitive	Light Sensitive
Stabilität	Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months.

Sicherheit

Kennzeichnung gefährlicher	Xn
R-Sätze:	22-37/38-41
S-Sätze:	26-36/39
WGK Germany	3

Gefahreninformationscode (GHS)

AR-A014418 Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R22:Gesundheitsschädlich beim Verschlucken.
R37/38:Reizt die Atmungsorgane und die Haut.
R41:Gefahr ernster Augenschäden.
S-Sätze Betriebsanweisung:
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S36/39:Bei der Arbeit geeignete Schutzkleidung und Schutzbrille/Gesichtsschutz tragen.
Beschreibung
AR-A 014418 (487021-52-3) is a selective glycogen synthase kinase 3 (GSK-3) inhibitor, IC50 = 104 nM. Inhibits β-amyloid-mediated neurodegeneration in hippocampal slices. Anti-inflammatory activity. Cell permeable. Active in rodent models.
Chemische Eigenschaften
Pale Yellow Solid
Verwenden
AR-A014418 has been used as an inhibitor of glycogen synthase kinase 3 (GSK3).
Verwenden
Glycogen Synthase Kinase 3β (GSK-3β) inhibitor.
Allgemeine Beschreibung
A cell-permeable thiazole-containing urea compound that acts as a potent inhibitor of GSK-3. Shown to inhibit GSK-3β with high potency (IC₅₀ = 104 nM). Inhibition is competitive with respect to ATP (K_i = 38 nM). Specificity has been reported using a panel of 28 different kinases, including Cdk2 and Cdk5 (IC₅₀ >100 μM). Shown to prevent tau phosphorylation at a GSK-3-specific site. Also shown to protect neuronal cells against Aβ-mediated neurodegeneration in vitro and reduce tauopathy in mice in vivo (30 μmol/kg delivered with 40% PEG400 and 40% dimethylacetamide in water). Caution: Do not use delivering vehicles containing dimethylamine for in vivo studies, as it is highly toxic to animals. A 25 mM (5 mg/649 μl) solution of GSK-3β Inhibitor VIII (Cat. No. 361557) in DMSO is also available.
Biochem/physiol Actions
Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase that has been implicated in pathological conditions such as diabetes and Alzheimer′s disease. GSK3 inhibitor, AR-A014418, inhibits GSK3 (IC50 = 104 nM), in an ATP-competitive manner (Ki = 38 nM). AR-A014418 does not significantly inhibit cdk2 or cdk5 (IC50 > 100 μM) or 26 other kinases, demonstrating high specificity for GSK3.
in vitro
ara014418 acted as an atp-competitive manner and did not significantly inhibit cdk2 or cdk5 or 26 other kinases demonstrating high specificity for gsk3. ar-a014418 inhibited tau phosphorylation at a gsk3-specific site (ser-396) in cells stably expressing human four-repeat tau protein [1].
in vivo
ara014418 induced behavioural changes that were consistent with the effects of antidepressant drugs. subacute intraperitoneal injections of ar-a014418 reduced immobility time in rats exposed to the forced swim test, which was a well-established model for antidepressant efficacy. moreover, the specificity of this effect was supported by our finding that ar-a014418 decreased spontaneous as well as amphetamine-induced activity [2].
Enzyminhibitor
This ATP-competitive protein kinase inhibitor (FW = 308.31 g/mol; CAS 487021-52-3; Solubility: 62 mg/mL DMSO; <1 mg/mL H2O) selectively targets glycogen synthase kinase 3β (GSK3β),with IC50 = 104 nM; Ki = 38 nM. Attesting to its high specificity for GSK3, AR-A014418 does not significantly inhibit Cdk2 or Cdk5 (IC50 > 100 μM) or 26 other kinases. AR-A014418 inhibits phosphorylation of the microtubule-associated protein Tau at Ser-396 (i.e., the GSK3-specific site) in cells stably expressing human four-repeat Tau. AR-A014418 protects N2A neuroblastoma cells against cell death mediated by inhibition of the phosphatidylinositol 3-kinase/protein kinase B survival pathway. AR- A014418 inhibits neurodegeneration mediated by b-amyloid peptide in hippocampal slices. Treatment of neuroblastoma cell lines with AR- A014418 reduced the level of GSK-3α phosphorylation at Tyr-279 compared to GSK-3β phosphorylation at Tyr-216, and attenuated growth via the maintenance of apoptosis.. AR-A014418-dependent antinociceptive effects are induced by modulation of the glutamatergic system through metabotropic and ionotropic (NMDA) receptors and the inhibition of TNF-α and IL-1β cytokine signaling.
IC 50
104 ± 27 nm
Lager
+4°C
Einzelnachweise
1) Bhat et al. (2003), Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418; J. Biol. Chem., 278 45937 2) Ramirez et al. (2010), Inhibition of glycogen synthase kinase 3beta (GSK3β) decreases inflammatory responses in brain endothelial cells; Am. J. Pathol., 176 881

AR-A014418 Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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